PMID- 9756939
OWN - NLM
STAT- MEDLINE
DCOM- 19981102
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 273
IP  - 41
DP  - 1998 Oct 9
TI  - Overexpressed activated retinoid X receptors can mediate growth inhibitory 
      effects of retinoids in human carcinoma cells.
PG  - 26915-22
AB  - Retinoic acid receptors (RARs) and retinoid X receptors (RXRs) mediate the 
      effects of retinoids on gene expression by binding to response elements in 
      retinoid-sensitive genes. RAR- but not RXR-selective retinoids were found in many 
      previous studies to suppress the growth of various cells, implicating RXR-RAR in 
      these effects. Using a co-expression vector for identifying cells that expressed 
      retinoid receptors transiently and 5'-bromo-2'-deoxyuridine incorporation for 
      labeling DNA-synthesizing cells, we found that RXR-selective retinoids inhibited 
      DNA synthesis in squamous carcinoma 1483 cells transfected with RXRalpha but not 
      with RARs. Ligand-induced transcription of the reporter luciferase gene via the 
      activation of RXR-RXR but not RXR-RAR correlated with growth suppression. Studies 
      with RXRalpha deletion mutants indicated that the DNA binding and the ligand 
      binding domains are essential for mediating growth inhibition. A point mutation 
      in the ligand binding domain (L430F) that decreased RXRalpha homodimerization 
      compromised its growth inhibitory function. Further, RXRalpha mutant (F313A), 
      which functions as a constitutively active receptor, inhibited DNA synthesis in 
      the absence of ligand. These results demonstrate that RXR homodimer activation 
      leads to growth inhibition and suggest that transfection of RXRalpha and 
      treatment with RXR-selective retinoids or the transfection of constitutively 
      activated RXRalpha mutant alone may have a therapeutic potential.
FAU - Wan, H
AU  - Wan H
AD  - Department of Tumor Biology, The University of Texas M. D. Anderson Cancer 
      Center, Houston, Texas 77030, USA.
FAU - Dawson, M I
AU  - Dawson MI
FAU - Hong, W K
AU  - Hong WK
FAU - Lotan, R
AU  - Lotan R
LA  - eng
GR  - P01 CA51993/CA/NCI NIH HHS/United States
GR  - P01 CA52051/CA/NCI NIH HHS/United States
GR  - P30 CA16672/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (DNA Primers)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Receptors, Retinoic Acid)
RN  - 0 (Retinoid X Receptors)
RN  - 0 (Transcription Factors)
RN  - 1UA8E65KDZ (Alitretinoin)
RN  - 5688UTC01R (Tretinoin)
SB  - IM
MH  - Alitretinoin
MH  - Base Sequence
MH  - Cell Division/drug effects
MH  - DNA Primers
MH  - DNA Replication
MH  - Dimerization
MH  - Humans
MH  - Nuclear Proteins/*metabolism
MH  - Receptors, Retinoic Acid/*metabolism
MH  - Retinoid X Receptors
MH  - Sequence Deletion
MH  - Transcription Factors/*metabolism
MH  - Transcriptional Activation
MH  - Tretinoin/pharmacology
MH  - Tumor Cells, Cultured
EDAT- 1998/10/03 00:00
MHDA- 1998/10/03 00:01
CRDT- 1998/10/03 00:00
PHST- 1998/10/03 00:00 [pubmed]
PHST- 1998/10/03 00:01 [medline]
PHST- 1998/10/03 00:00 [entrez]
AID - S0021-9258(19)59829-5 [pii]
AID - 10.1074/jbc.273.41.26915 [doi]
PST - ppublish
SO  - J Biol Chem. 1998 Oct 9;273(41):26915-22. doi: 10.1074/jbc.273.41.26915.